Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids.

The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates [DAPs]), including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans-chrysanthemumdicarboxylic acid, and 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NEOs. The median and maximum concentrations of the sum of the seven NEOs (ΣNEO) were 4.7 and 370.2nmol/g creatinine, respectively. Urinary ΣNEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p<0.05). The creatinine-adjusted concentration of ΣNEO significantly correlated with those of all DAPs (p<0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary ΣDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs are common to those of OPs.

A revised method for determination of dialkylphosphate levels in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: application to human urine samples from Japanese children.

OBJECTIVES: Biological monitoring of organophosphorus insecticide (OP) metabolites, specifically dialkylphosphates (DAP) in urine, plays a key role in low-level exposure assessment of OP in individuals. The aims of this study are to develop a simple and sensitive method for determining four urinary DAPs using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS), and to assess the concentration range of urinary DAP in Japanese children. METHODS: Deuterium-labeled DAPs were used as internal standards. Urinary dimethylphosphate (DMP) and diethylphosphate (DEP), which passed through the solid-phase extraction (SPE) column, and dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP), which were extracted from a SPE column using 2.5 % NH3 water including 50 % acetonitrile, were prepared for separation analysis. The samples were then injected into LC-MS/MS. The optimized method was applied to spot urine samples from 3-year-old children (109 males and 116 females) living in Aichi Prefecture in Japan. RESULTS: Results from the validation study demonstrated good within- and between-run precisions (<10.7 %) with low detection limits (0.4 for DMP and DMTP, 0.2 for DEP and 0.1 µg/L for DETP). The geometric mean values and detection rates of the urinary DAPs in Japanese children were 14.4 µg/L and 100 % for DMP, 5.3 µg/L and 98 % for DMTP, 5.5 µg/L and 99 % for DEP, and 0.6 µg/L and 80 % for DETP, respectively. CONCLUSIONS: The present high-throughput method is simple and reliable, and can thereby further contribute to development of an exposure assessment of OP. The present study is the first to reveal the DAP concentrations in young Japanese children.